The Antiproliferative Potency of Histamine Antagonists Correlates with Inhibition of Binding of [3H]-Histamine to Novel Intracellular Receptors (HIC) in Microsomal and Nuclear Fractions of Rat Liver

H3 receptor antagonist, thioperamide, inhibits adrenal steroidogenesis and histamine binding to adrenocortical microsomes and binds to cytochrome P450

“…However, in our studies these inhibitors have consistently failed to block basal or ACTH-stimulated secretion of cortisol from isolated adrenal cells. It remains to be determined whether or not preformed histamine in adrenocortical cells plays a physiological role in the modulation of P450 enzymes of steroidogenesis, as we suggested for modulation of growth and proliferation of lymphocytes and cultured cells (Brandes et al, 1991;Brandes & LaBella, 1992).…”

“…binding sites in microsomes from several tissues and the potency to inhibit platelet aggregation (Brandes et al, 1990;1991). P450 inhibitors also block aggregation (Parnham et al, 1981), suggesting a close association between HIc and P450 in platelets.…”

“…A low affinity (jaM) site in microsomes has been implicated in a second messenger role for histamine in platelets (Saxena et al, 1989); additional high and low affinity nuclear sites, of different ligand specificity, appear to play a growth-modulatory role in lymphocytes (Brandes et al, 1990;1991). H1c exhibits strong preference for certain novel, antioestrogen-like compounds, lesser affinity for HI ligands and very low affinity for H2 ligands (Brandes et al, 1990).…”

Hormones in the nucleus. Immunologically demonstrable biogenic amines (serotonin, histamine) in the nucleus of rat peritoneal mast cells

“…Arkhipova et al (1988) described that the rate of RNA synthesis in the nuclear fraction of rat brain in vitro depends on the concentrations of amines, serotonin included. According to Brandes et al (1990Brandes et al ( , 1991, histamine is an intracellular messenger and they found histamine binding sites in the nucleus of rat liver. These latter observations seems to be especially important as they can give us some explanation on the role of amines in the nucleus.…”

Risk of non-Hodgkin lymphoma in relation to tricyclic antidepressant use

“…35 HIC is also thought to promote the growth of transformed lymphocytes by inhibiting normal lymphocyte proliferation, which decreases suppressor T-lymphocyte function. 36,37 Based on these findings, it seems that if antihistamines do influence lymphoma risk, the mechanism(s) by which they do so could include effects on either the early stages of lymphomagenesis, on later stages as a promoter, or both.…”